Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
1.
Eur Rev Med Pharmacol Sci ; 27(14): 6472, 2023 07.
Article in English | MEDLINE | ID: mdl-37522656

ABSTRACT

The article "Lixisenatide protects doxorubicin-induced renal fibrosis by activating wNF-κB/TNF-α and TGF-ß/Smad pathways", by N.-F. Guo, Y.-J. Cao, X. Chen, Y. Zhang, Y.-P. Fan, J. Liu, X.-L. Chen published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 4017-4026. DOI: 10.26355/eurrev_201905_17832-PMID: 31115031 has been retracted by the Editor in Chief for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/983F02C9C18817139AE18497C359FA). In particular, concerns were raised about Figures 2A and 5A as the figures result to overlap with previously published papers. The Editorial Office has contacted the corresponding author of the article to provide a reply to the comments on PubPeer and check the raw data. Still, the journal has yet to receive a reply. Therefore, considering the comments released on PubPeer and the lack of response from authors, the Editor in Chief no longer relies on the data presented and decided to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17832.

5.
Eur Rev Med Pharmacol Sci ; 23(9): 4017-4026, 2019 May.
Article in English | MEDLINE | ID: mdl-31115031

ABSTRACT

OBJECTIVE: The aim of this study was to investigate whether Lixisenatide, NF-kB/TNF-α, and TGF-ß/Smad pathways exert clear regulatory roles in doxorubicin-induced renal fibrosis in rats, and to explore the possible underlying mechanism. MATERIALS AND METHODS: 30 rats were randomly assigned into the sham group, the Doxorubicin (DOX) group and the Lixisenatide group, 10 in each group. Eight weeks after the specific animal procedure, serum and kidney samples of rats were collected. The serum levels of Cr and BUN were detected using relative commercial kits. The activities of malondialdehyde (MDA), total antioxidant capacity (T-AOC), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD) in kidney homogenate were accessed using commercial kits. Meanwhile, pathological lesions in kidney tissues were evaluated by HE staining, immune-histochemical staining and TUNEL assay, respectively. Also, the protein levels of relative genes in NF-kB/TNF-α, and TGF-ß/Smad pathways in rat kidneys were determined by immune-histochemical staining and Western blot, respectively. RESULTS: Rats in the Lixisenatide group showed significantly lower levels of Cr and BUN. Activities of T-AOC, CAT, GSH, and SOD in the Lixisenatide group were significantly higher, whereas MDA activity was significantly lower than in the DOX group. Lixisenatide treatment remarkably alleviated DOX-induced pathological lesions and cell apoptosis in kidneys. Furthermore, the protein levels of relative genes in NF-kB/TNF-α and TGF-ß/Smad pathways in rat kidneys were significantly downregulated in the Lixisenatide group when compared with the DOX group. CONCLUSIONS: Lixisenatide protects doxorubicin-induced renal fibrosis in rats by inhibiting NF-κB/TNF-α and TGF-ß/Smad pathways.


Subject(s)
Kidney Diseases/pathology , Peptides/therapeutic use , Protective Agents/therapeutic use , Signal Transduction , Animals , Antioxidants/metabolism , Doxorubicin/toxicity , Glutathione/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Male , NF-kappa B/metabolism , Neutrophil Infiltration , Peptides/pharmacology , Protective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Smad Proteins/metabolism , Superoxide Dismutase/metabolism , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/metabolism
6.
Eur Rev Med Pharmacol Sci ; 22(12): 3763-3770, 2018 06.
Article in English | MEDLINE | ID: mdl-29949151

ABSTRACT

OBJECTIVE: Previous studies have shown that BC029135, a long noncoding RNA (lncRNA) with high conservation, was decreased with high fold change in colorectal cancer (CRC) by using microarray assay. In the present work, we investigated the functions of BC029135 in CRC, as well as the potential mechanisms underlying the malignant phenotype caused by loss of BC029135. MATERIALS AND METHODS: Bioinformatics analysis of lncRNA BC029135 was performed to identify the potential function. The cell lines of HCT-116, SW480, SW620, LoVo, SW1116, and HT29 were used in this study. The mRNA expression of BC029135 and ß-actinin was measured by Real-Time Polymerase Chain Reaction (RT-PCR). Western blot analysis was used to determine protein expression of ß-actinin, MMP-2, cyclin D1, and c-Myc. RESULTS: Our research showed that the expression of BC029135 in CRC tissues and cell lines was significantly lower than in adjacent normal tissues. In addition, overexpression of lncRNA BC029135 could inhibit the invasion of CRC cells. We also found that lncRNA BC029135 inhibits Wnt/ß-catenin signaling in CRC cell lines. CONCLUSIONS: We suggest that up-regulation of BC029135 suppresses CRC invasion and inactivates Wnt/ß-catenin signaling. It will provide new insights for the treatment of colorectal cancer and new clues for clinical treatment.


Subject(s)
Colorectal Neoplasms/metabolism , RNA, Long Noncoding/biosynthesis , Wnt Signaling Pathway/physiology , beta Catenin/metabolism , Aged , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , HCT116 Cells , HT29 Cells , Humans , Male , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/prevention & control , RNA, Long Noncoding/genetics , beta Catenin/antagonists & inhibitors , beta Catenin/genetics
7.
Allergy ; 73(2): 459-469, 2018 02.
Article in English | MEDLINE | ID: mdl-28771767

ABSTRACT

BACKGROUND: IL-25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the association of IL-25 with the Th2-biased inflammatory profiles in CRSwNP. METHODS: Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL-25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT-qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL-25high and IL-25low ) were evaluated, and the effects of IL-25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro. RESULTS: The mRNA and protein levels of IL-25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL-25high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL-25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro. CONCLUSIONS: Local IL-25 plays a crucial role in promoting Th2-biased inflammatory profiles in NP and may serve as a promising therapeutic target in CRSwNP patients.


Subject(s)
Inflammation/immunology , Interleukin-17/genetics , Interleukin-17/immunology , Nasal Polyps/genetics , Nasal Polyps/immunology , Th2 Cells/immunology , Adult , China , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Immunohistochemistry , Inflammation/complications , Inflammation/genetics , Male , Nasal Polyps/complications , Polymerase Chain Reaction
8.
Epidemiol Infect ; 145(9): 1843-1851, 2017 07.
Article in English | MEDLINE | ID: mdl-28351443

ABSTRACT

Pig farmers and veterinarians have high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) due to the occupational livestock exposure, while few reported this association on slaughterhouse workers. We conducted this cross-sectional study to explore the phenotypic and molecular characteristics of S. aureus and MRSA in slaughterhouse pig-related workers and control workers in Guangdong Province, China. Participants were interviewed and provided two nasal swabs. Swabs were tested for S. aureus, and isolates were further tested for antimicrobial susceptibility, virulence genes and multi-locus sequence typing. Compared with control workers, pig-related workers have significantly higher prevalence of MRSA carriage (adjusted odd ratio (aOR) 3·70, 95% CI 1·63-8·40). The proportions of MRSA resistant to clindamycin, erythromycin, tetracycline or chloromycetin were significantly higher in pig-related workers than in control workers. The predominant phenotypes of S. aureus were resistant to penicillin, clindamycin, erythromycin and tetracycline. Three MRSA CC9 isolates with livestock-associated characteristics (resistance to tetracycline and absence of immune evasion cluster (IEC) genes) were detected in pig-related workers but not in control workers. For human-associated CCs (CC7, CC59, CC6, and CC188), there was no significant difference in IEC profile or antimicrobial resistance between the groups. These findings reveal that there may be a potential risk for livestock-to-human transmission of LA-MRSA and human-to-human transmission of human-associated MRSA.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Occupational Diseases/epidemiology , Staphylococcal Infections/epidemiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Abattoirs , Adolescent , Adult , China/epidemiology , Female , Humans , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/physiology , Middle Aged , Occupational Diseases/microbiology , Prevalence , Staphylococcal Infections/microbiology , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Young Adult
9.
Mol Biol Rep ; 39(9): 8733-40, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22722989

ABSTRACT

Stearoyl-CoA desaturase (SCD) is a multifunctional complex enzyme important in the cellular biosynthesis of fatty acids. The present study was to investigate the association of the SCD gene with milk production traits in dairy cattle. Two single nucleotide polymorphisms (SNPs) (g.6926A>G and g.8646A>G) in introns 3 and 4, and three SNPs (g.10153A>G, g.10213T>C and g.10329C>T) in exon 5 were identified with pooled DNA sequencing and genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry assay in 752 Chinese Holstein cows. Polymorphism g.10329C>T was predicted to result in an amino acid replacement from alanine to valine in the SCD protein. With a mixed animal model, the significant associations of the five SNPs with 305-day milk, fat and protein yields and protein percentage were determined. We further demonstrated cows with heterozygous genotypes (A/G or C/T) had highest 305 day milk yield, fat yield, protein yield and lowest protein percentage. Heterozygous cows with genotype AG at the g.6926A>G locus showed the greatest milk yield (P < 0.0001), fat yield (P < 0.0001) and protein yield (P < 0.0001) among other heterozygous genotypes at any of the loci. Dominance effects of all identified SNPs on milk, fat and protein yields and protein percentage were significant. Moreover, significant allele substitution effects at g.6926A>G locus on milk yield and at g.10213T>C on protein yield were observed. Five-locus haplotypes and strong linkage disequilibrium (D' > 0.9) between the five SNPs were also observed. The results suggest that identified polymorphisms could be potential genetic markers to improve the production performance of Chinese Holstein.


Subject(s)
Cattle/genetics , Lactation/genetics , Milk , Polymorphism, Single Nucleotide , Quantitative Trait, Heritable , Stearoyl-CoA Desaturase/genetics , Alleles , Animals , China , Female , Gene Frequency , Gene Order , Genotype , Linkage Disequilibrium , Phenotype
10.
Eur J Cancer Care (Engl) ; 20(5): 620-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21410802

ABSTRACT

Breast cancer is one of the main causes of death for women throughout the world. The objective of this study is to identify significant factors of patients and their tumours that can be used to predict a 5-year survival status for Asian women. Patients who had been diagnosed with invasive breast carcinoma and undergone mastectomy were selected (n= 1016). Patient characteristics and outcome variables were also retrieved. A nomogram was created and its performance was evaluated by calculating its discrimination (concordance index), calibration, and by subsequent internal validation. The median follow-up was 39 months and mean overall survival was 62.5 months. Independent predictors of overall survival included in the nomogram were age, tumour size, lymph node involvement, metastasis and oestrogen receptor status. The concordance index was 0.80 and the calibration was excellent with all observed outcomes within the 95% CI of each predicted survival probability. The nomogram model was developed to predict the probability of survival in patients with breast cancer and should be useful for counselling patients and establishing appropriate surveillance strategies for Asian women.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Nomograms , Aged , Cohort Studies , Disease-Free Survival , Female , Humans , Middle Aged , Predictive Value of Tests , Prognosis , Survival Analysis , Taiwan/epidemiology , Time Factors
11.
Theriogenology ; 71(3): 412-21, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18789518

ABSTRACT

The objective was to explore mechanisms of the influence of porcine cumulus cells (CC) on oocyte maturation. Immature porcine oocytes were matured in groups of denuded oocyte (DOs), cumulus-oocyte complexes (COCs), denuded oocytes co-cultured with CC (DoCC), or with cumulus-oocyte complexes (DoCOCs). Ooplasmic mitochondria-lipid distributions, glutathione (GSH)-adenosine triphosphate (ATP) contents, calcium release pattern, and developmental competence after parthenogenetic activation were assessed after IVM. The portion of matured oocytes after IVM and the developmental competence and GSH content in single oocytes were lower in DOs than in COCs (P<0.05). In contrast, the maturation rate and development in DoCOCs and COCs were higher than in DoCC and DOs (P<0.05). The blastocyst rate in DoCOCs was higher than in DOs (P<0.05), and ATP content in COCs was higher than in all other groups (P<0.01). In addition, the rate of oocytes with damaged oolemma in DOs (35%) was significantly higher than in COCs (3%), DoCOCs (7%), and DoCC (10%). The rate of oocytes with evenly distributed mitochondria was 70% in DOs, which was significantly lower than in COCs and DoCC (89 and 84%, respectively). The percentage of oocytes with normal lipid droplets distributions in COCs (70%) was significantly higher than in three other groups, whereas both percentages in DoCC and DoCOCs were higher than in DOs (P<0.05). The duration of [Ca(2+)] rise in DOs was longer than in three other groups, whereas the duration was shortest in COCs. The amplitude of the [Ca(2+)] rise in DOs was significantly lower than in other groups (P<0.05), but the amplitude did not differ significantly among DoCC, DoCOCs and COCs. In conclusion, the presence of porcine CC during IVM functionally affected ooplasmic mitochondria-lipid distributions and GSH-ATP contents, which may affect the calcium release pattern and developmental competence of oocytes after electro-activation.


Subject(s)
Adenosine Triphosphate/metabolism , Calcium/metabolism , Cumulus Cells/physiology , Glutathione/metabolism , Mitochondria/physiology , Swine/physiology , Animals , Cytoplasm/physiology , Female , Lipid Metabolism , Oocytes/cytology , Oocytes/physiology
12.
J Nutr Health Aging ; 9(4): 203-10, 2005.
Article in English | MEDLINE | ID: mdl-15980920

ABSTRACT

OBJECTIVES: To develop and validate a nutritional screening tool (CNS) for elderly Chinese subjects in the institutional setting. DESIGN: Using the MNA as a guide, a questionnaire was developed appropriate for the Chinese health care system, diet, food customs and culture, using physician assessment for comparison. PARTICIPANTS: 200 men and 200 women aged 65 years or older, approximately equally distributed by age between two cities in China (Hong Kong and Shanghai), were recruited from hospitals and old age homes for the reliability study. 340 men and 527 women were recruited for the validity study. RESULTS: The CNS compared with physician assessments based on two groups, normal or at risk with less than normal nutritional status, had kappa coefficients of 0.5 overall and were as high as 0.8 in Shanghai. CNS was able to identify about 90% of all persons with normal nutritional status and had about a 60% chance of correctly identifying a person at risk with a less than normal nutritional status. CONCLUSION: The CNS can be used in a 2-group classification to identify those who have a normal nutritional status (CNS > or = 21). Those who do not fall into this group should have their nutritional status evaluated in greater detail (CNS score < or = 20). The applicability of screening tools may vary depending on the site and the population characteristics.


Subject(s)
Geriatric Assessment/methods , Mass Screening/organization & administration , Mass Screening/standards , Nutrition Assessment , Nutrition Disorders/diagnosis , Aged , Aged, 80 and over , Female , Homes for the Aged , Hospitalization , Humans , Male , Nutritional Status , ROC Curve , Risk Assessment , Sensitivity and Specificity , Surveys and Questionnaires , Weight Loss
13.
Am J Physiol Gastrointest Liver Physiol ; 280(1): G32-42, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11123195

ABSTRACT

We examined the effect of endotoxin lipopolysaccharide (LPS) on the basal tone and on the effects of different stimuli and agonists and transcriptional and translational expression of nitric oxide (NO) synthase (NOS) isozymes in the lower esophageal sphincter (LES), pyloric sphincter (PS), and internal anal sphincter (IAS). NO release was also examined before and after LPS. LPS caused a dose-dependent fall in the basal tone and augmentation of the relaxation caused by nonadrenergic, noncholinergic (NANC) nerve stimulation in the LES and IAS. In the PS, LPS had no significant effect on the basal tone and caused an attenuation of the NANC relaxation and an augmentation of the contractile response of muscarinic agonist. Interestingly, the smooth muscle relaxation by atrial natriuretic factor was suppressed in the LES and IAS but not in the PS. These changes in the sphincteric function following LPS may be associated with increase in the inducible NOS (iNOS) expression since they were blocked by iNOS inhibitor L-canavanine. Augmentation of NANC relaxation in the LES and IAS smooth muscle by LPS may be due to the increased activity of neuronal NOS and NO production.


Subject(s)
Esophageal Diseases/metabolism , Esophagogastric Junction/enzymology , Esophagogastric Junction/physiopathology , Nitric Oxide Synthase/metabolism , Anal Canal/enzymology , Anal Canal/innervation , Anal Canal/physiopathology , Animals , Atrial Natriuretic Factor/pharmacology , Bethanechol/pharmacology , Electric Stimulation , Enteric Nervous System/drug effects , Enteric Nervous System/physiology , Esophageal Diseases/chemically induced , Esophageal Diseases/physiopathology , Esophagogastric Junction/innervation , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/physiology , Isoproterenol/pharmacology , Lipopolysaccharides/pharmacology , Muscle Tonus/drug effects , Muscle Tonus/physiology , Muscle, Smooth/enzymology , Muscle, Smooth/innervation , Muscle, Smooth/physiopathology , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type I , Nitric Oxide Synthase Type II , Nitroprusside/pharmacology , Norepinephrine/metabolism , Opossums , Parasympathomimetics/pharmacology , Phenylephrine/pharmacology , Pylorus , Sympathomimetics/pharmacology , Tetrodotoxin/pharmacology , Vasoactive Intestinal Peptide/pharmacology , Vasodilator Agents/pharmacology
14.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 21(6): 406-8, 2001 Jun.
Article in Chinese | MEDLINE | ID: mdl-12577430

ABSTRACT

OBJECTIVE: To observe the antifebrile effect of Naoreqing (NRQ) oral liquid on fever in patients after glioma or meningioma operation. METHODS: Patients were divided into 3 groups, the TCM group treated with NRQ, the TCM-WM group treated with NRQ plus western medicine and the WM group treated with western medicine alone. The treatment was applied for 7 successive days. The mean time of fever and fever subsidence, body temperature before and after treatment were recorded and compared. RESULTS: The antifebrile effect in the TCM and the TCM-WM group was superior to that in the WM group significantly (P < 0.01), and the difference between the TCM group and the TCM-WM group was insignificant. CONCLUSION: NRQ can evidently reduce the body temperature of patients after brain tumor operation, its antifebrile effect is irrelevant to the kind of tumor being glioma or meningioma.


Subject(s)
Brain Neoplasms/surgery , Drugs, Chinese Herbal/therapeutic use , Fever/drug therapy , Glioma/surgery , Phytotherapy , Postoperative Complications/drug therapy , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Meningeal Neoplasms/surgery , Meningioma/surgery , Middle Aged
15.
J Neurophysiol ; 84(6): 2896-903, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11110819

ABSTRACT

Neurons in the caudal hypothalamus (CH) are responsible for the modulation of various processes including respiratory and cardiovascular output. Previous results from this and other laboratories have demonstrated in vivo that these neurons have firing rhythms matched to the respiratory and cardiovascular cycles. The goal of the present study was to characterize the biophysical properties of neurons in the CH with particular emphasis in those properties responsible for rhythmic firing behavior. Whole cell, patch-clamped CH neurons displayed a resting membrane potential of -58.0 +/- 1.1 mV and an input resistance of 319.3 +/- 16.6 MOmega when recorded in current-clamp mode in an in vitro brain slice preparation. A large proportion of these neurons displayed postinhibitory rebound (PIR) that was dependent on the duration and magnitude of hyperpolarizing current as well as the resting membrane potential of the cell. Furthermore these neurons discharged tonically in response to a depolarizing current pulse at a depolarized resting membrane potential (more positive than -65 mV) but switched to a rapid burst of firing to the same stimulus when the resting membrane potential was lowered. The PIR observed in these neurons was calcium dependent as demonstrated by the ability to block its amplitude by perfusion of Ca(2+)-free bath solution or by application of Ni(2+) (0.3-0.5 mM) or nifedipine (10 microM). These properties suggest that low-voltage-activated (LVA) calcium current is involved in the PIR and bursting firing of these CH neurons. In addition, high-voltage-activated calcium responses were detected after blockade of outward potassium current or in Ba(2+)-replacement solution. In addition, almost all of the CH neurons studied showed spike frequency adaptation that was decreased following Ca(2+) removal, indicating the involvement of Ca(2+)-dependent K(+) current (I(K,Ca)) in these cells. In conclusion, CH neurons have at least two different types of calcium currents that contribute to their excitability; the dominant current is the LVA or T-type. This LVA current appears to play a significant role in the bursting characteristics that may underlie the rhythmic firing of CH neurons.


Subject(s)
Calcium Channels/metabolism , Hypothalamus, Posterior/physiology , Neurons/physiology , Action Potentials/drug effects , Animals , Barium/pharmacology , Calcium/metabolism , Calcium/pharmacology , Calcium Channel Blockers/pharmacology , Cell Hypoxia/physiology , Electric Stimulation , Hypothalamus, Posterior/cytology , Hypothalamus, Posterior/drug effects , In Vitro Techniques , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neurons/cytology , Neurons/drug effects , Nickel/pharmacology , Nifedipine/pharmacology , Patch-Clamp Techniques , Periodicity , Potassium Channel Blockers , Potassium Channels/metabolism , Rats , Rats, Sprague-Dawley , Tetrodotoxin/pharmacology , gamma-Aminobutyric Acid/metabolism , gamma-Aminobutyric Acid/pharmacology
16.
Am J Physiol ; 277(1): G152-60, 1999 07.
Article in English | MEDLINE | ID: mdl-10409162

ABSTRACT

Cholera toxin (CTX), an activator of G(s) protein, is an important pharmacological tool in G protein research. The effect and the mechanism of action of CTX in the gastrointestinal smooth muscle, including the internal anal sphincter (IAS), are not known. The present investigation was carried out to examine the effects of CTX on the signal transduction associated with the adenylate cyclase (AC) pathway on the basal tone of the IAS smooth muscle. CTX caused a prompt and dose-dependent fall in the basal tone of the IAS that was not affected by the neurotoxins TTX and omega-conotoxin or the nitric oxide synthase inhibitor N(G)-nitro-L-arginine. The cyclooxygenase inhibitor indomethacin, cAMP-dependent protein kinase inhibitor Rp-8-bromoadenosine 3',5' cyclic monophosphorothioate inhibited CTX-induced IAS smooth muscle relaxation. Furthermore, CTX caused a concentration-dependent relaxation of the isolated smooth muscle cells (SMC) of the IAS, which was blocked by G(s)alpha antibody (G(s)alpha-Ab). The IAS smooth muscle relaxation was accompanied with an increase in the GTPase activity that was also specifically blocked by G(s)alpha-Ab. We conclude that a major part of the inhibitory action of CTX in the IAS is via the direct response of the SMC that is linked with G(s) protein to the AC pathway. A part of the inhibitory action of CTX on the smooth muscle occurs via the activation of cyclooxygenase pathway. The relative contribution of such actions of CTX in the smooth muscle in the gastrointestinal motility disturbances following cholera infection remains to be determined.


Subject(s)
Anal Canal/drug effects , Cholera Toxin/pharmacology , Muscle, Smooth/drug effects , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Animals , Cyclooxygenase Inhibitors/pharmacology , Enzyme Inhibitors/pharmacology , Female , GTP Phosphohydrolases/metabolism , In Vitro Techniques , Indomethacin/pharmacology , Male , Muscle Tonus/drug effects , Nitric Oxide Synthase/antagonists & inhibitors , Nitroarginine/pharmacology , Opossums , Peptides/pharmacology , Tetrodotoxin/pharmacology , omega-Conotoxin GVIA
17.
J Neurophysiol ; 81(4): 1949-59, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10200229

ABSTRACT

Previous reports from this laboratory have shown that a high percentage of neurons in the caudal hypothalamus are stimulated by hypoxia both in vivo and in vitro. This stimulation is in the form of an increase in firing frequency and significant membrane depolarization. The goal of the present study was to determine if this hypoxia-induced excitation is influenced by development. In addition, we sought to determine the mechanism by which hypoxia stimulates caudal hypothalamic neurons. Caudal hypothalamic neurons from neonatal (4-16 days) or juvenile (20-40 days) rats were patch-clamped, and the whole cell voltage and current responses to moderate (10% O2) or severe (0% O2) hypoxia were recorded in the brain slice preparation. Analysis of tissue oxygen levels demonstrated no significant difference in the levels of tissue oxygen in brain slices between the different age groups. A significantly larger input resistance, time constant and half-time to spike height was observed for neonatal neurons compared with juvenile neurons. Both moderate and severe hypoxia elicited a net inward current in a significantly larger percentage of caudal hypothalamic neurons from rats aged 20-40 days (juvenile) as compared with rats aged 4-16 days (neonatal). In contrast, there was no difference in the magnitude of the inward current response to moderate or severe hypoxia between the two age groups. Those cells that were stimulated by hypoxia demonstrated a significant decrease in input resistance during hypoxic stimulation that was not observed in those cells unaffected by hypoxia. A subset of neurons were tested independent of age for the ability to maintain the inward current response to hypoxia during synaptic blockade (11.4 mM Mg2+/0. 2 mM Ca2+). Most of the neurons tested (88.9%) maintained a hypoxic excitation during synaptic blockade, and this inward current response was unaffected by addition of 2 mM cobalt chloride to the bathing medium. In contrast, perfusion with the Na+ channel blocker, tetrodotoxin (1-2 microM) or Na+ replacement with N-methyl-D-glucamine (NMDG) significantly reduced the inward current response to hypoxia. Furthermore, the input resistance decrease observed during hypoxia was attenuated significantly during perfusion with NMDG. These results indicate the excitation elicited by hypoxia in hypothalamic neurons is age dependent. In addition, the inward current response of caudal hypothalamic neurons is not dependent on synaptic input but results from a sodium-dependent conductance.


Subject(s)
Hypothalamus/cytology , Hypoxia, Brain/physiopathology , Hypoxia/physiopathology , Neurons/physiology , Age Factors , Animals , Calcium/pharmacology , Cell Size/physiology , Cobalt/pharmacology , Fluorescent Dyes , Hypothalamus/growth & development , Isoquinolines , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neurons/cytology , Oxygen/analysis , Oxygen/metabolism , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Tetrodotoxin/pharmacology
18.
Am J Physiol ; 276(1): G138-45, 1999 01.
Article in English | MEDLINE | ID: mdl-9886989

ABSTRACT

The putative heme oxygenase inhibitor zinc protoporphyrin IX (ZnPP IX) is known to exert diverse actions, including inhibitory action on smooth muscle relaxation by vasoactive intestinal polypeptide (VIP). The studies were performed in the opossum lower esophageal sphincter (LES) smooth muscle to determine the site of the inhibitory action of ZnPP IX in the smooth muscle relaxation by VIP. We also examined the effect of a direct Gs protein activator, cholera toxin (CTX), known to stimulate adenylate cyclase (AC). CTX caused relaxation of the LES smooth muscle by its action directly at the smooth muscle cells. The convergence of the common mechanisms of actions of VIP and CTX on AC was determined by the suppression of their effects by the AC inhibitor and CTX desensitization. ZnPP IX caused attenuation of the LES smooth muscle relaxation by VIP but not by CTX. ZnPP IX but not zinc deuteroporphyrin IX caused significant inhibition of VIP binding to the membrane receptor. We conclude that ZnPP IX attenuates VIP-induced LES smooth muscle relaxation by inhibition of VIP binding to G protein-coupled receptors linked to AC at a point proximal to G protein activation.


Subject(s)
Enzyme Inhibitors/pharmacology , Esophagogastric Junction/drug effects , Heme Oxygenase (Decyclizing)/antagonists & inhibitors , Muscle Relaxation/drug effects , Protoporphyrins/pharmacology , Vasoactive Intestinal Peptide/pharmacology , Adenylyl Cyclase Inhibitors , Animals , Cholera Toxin/pharmacology , Deuteroporphyrins/pharmacology , Electric Stimulation , Female , In Vitro Techniques , Male , Muscle, Smooth/drug effects , Myenteric Plexus/physiology , Neurons/physiology , Opossums , Receptors, Vasoactive Intestinal Peptide/metabolism , Vasoactive Intestinal Peptide/metabolism
19.
J Pharmacol Exp Ther ; 285(2): 468-74, 1998 May.
Article in English | MEDLINE | ID: mdl-9580585

ABSTRACT

This study was performed in the opossum lower esophageal sphincter (LES) smooth muscle strips to determine the action of the heme oxygenase inhibitor zinc protoporphyrin IX (ZnPP IX) on the relaxant effect of vasoactive intestinal polypeptide and isoproterenol, which are known to stimulate adenylate cyclase (AC) via G protein coupling, and of the direct activator of AC catalytic subunit forskolin. To investigate the cGMP pathway, we examined the effect of atrial natriuretic factor known to activate the receptor linked to the particulate guanylate cyclase via G protein coupling and that of sodium nitroprusside [nitric oxide (NO) donor], authentic NO and carbon monoxide, which stimulate the intracellular soluble fraction of GC. The smooth muscle relaxation caused by nonadrenergic noncholinergic (NANC) nerve stimulation also was investigated. ZnPP IX caused concentration-dependent attenuation of the relaxant effect of vasoactive intestinal polypeptide, isoproterenol and atrial natriuretic factor without any effect on that of forskolin, sodium nitroprusside, NO and CO. Interestingly, ZnPP IX had no significant effect on the LES relaxation caused by NANC nerve stimulation and the smooth muscle contraction by bethanechol. From these results, we conclude that ZnPP IX attenuates the LES smooth muscle relaxation caused by the stimulation of G protein-coupled receptors to particulate AC and guanylate cyclase. The lack of effect of ZnPP IX on the NANC nerve-mediated LES relaxation suggests either lack of a role of heme oxygenase pathway in the response or an upregulation of NOS leading to normal LES relaxation.


Subject(s)
Esophagogastric Junction/drug effects , Muscle Relaxation/drug effects , Protoporphyrins/pharmacology , Vasoactive Intestinal Peptide/pharmacology , Animals , Bethanechol/pharmacology , Carbon Monoxide/metabolism , Colforsin/pharmacology , Esophagogastric Junction/physiology , Heme Oxygenase (Decyclizing)/physiology , In Vitro Techniques , Isoproterenol/pharmacology , Nitric Oxide/physiology , Opossums
20.
Aust Health Rev ; 20(4): 27-39, 1997.
Article in English | MEDLINE | ID: mdl-10178128

ABSTRACT

The study reported in this paper examined the characteristics of elderly people undergoing cataract surgery and compared patient perspectives and satisfaction, outcome, costs, reported health problems and social circumstances of day surgery patients and hospital inpatients. The study sample was drawn from the client database of a health insurance fund and covered 291 people aged 60 years or more who had recently undergone cataract surgery. Overall, both day surgery patients and inpatients indicated a high level of satisfaction with their eye surgery (about 80 per cent for both groups). The majority of patients from both groups reported an improved level of vision, with vision outcome in the day surgery group being as good as in the inpatient group. Overall, inpatient treatment was more costly and involved higher out of pocket expenses. The study results indicate a potential to increase the number of patients undergoing cataract surgery as a day patient procedure. Pre-operative preparation contributed to patient satisfaction and the availability of family and/or social support was an important factor influencing day surgery admission. Whilst patients reporting health problems were less inclined to have cataract surgery than were day patients, this only accounted for one-fifth of the total inpatient group. Developing systematic and appropriate case selection criteria and effective case management will contribute to more efficient use of hospital resources, an increased use of day surgery facilities, and hence a more cost-effective overall cataract surgery service for elderly people.


Subject(s)
Cataract Extraction/standards , Inpatients/psychology , Outpatients/psychology , Patient Satisfaction/statistics & numerical data , Aged , Aged, 80 and over , Ambulatory Surgical Procedures/economics , Ambulatory Surgical Procedures/standards , Australia , Case Management , Cataract Extraction/economics , Female , Health Care Costs , Health Status , Hospital Charges , Humans , Male , Middle Aged , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...